The effectiveness and high cost of current drug screening approaches are two major factors that challenge the pharmaceutical industry. The cost of bringing a single drug to the market is now estimated at about 1 billion dollars. 40 to 70% of this total development cost is invested in the pre-clinical and clinical stages. This high cost is due to the high number of failed drugs where two dominant factors for failure are lack of efficacy, and toxicity.
In vitro organ models hold a great promise as more physiological relevant platforms in drug screening than traditional approaches based on animal tests. Therefore, the ability to generate human tissue mimicries that represent basic tissue functional structures, such as hepatic acinus in the liver, nephrons in the kidney, is of benefit for drug screening as well as diverse applications in tissue engineering and regenerative medicine.
Despite the intense research on generating such platforms, a number of challenges constrains the bioengineering of organ models for practical applications including (1) organization of cells and their surrounding microenvironments with microscale resolution in the bioengineered tissue functional units; (2) sufficient vascularization inside tissue functional units for minimization of necrosis and loss of function; (3) need for high throughput generation of complex 3D repeating units.
Many tissues in the human body are composed of densely-packed cells and low extracellular matrix (ECM). For example, liver tissue, hepatocytes and endothelial cells constitute most of liver wet weight while ECM contributes approximately 0.5-3% of the total wet weight. The cell proximity is important to retain hepatocyte viability and form liver-specific functions.
Currently most of the methods developed for in vitro formation of liver tissue utilize scaffolds for cell homing. Scaffolds used in liver tissue engineering dramatically decrease cell-cell interactions that are critical for maintaining the functionality of the hepatocytes. Accordingly, tissue-engineering technologies mimicking cell-packing density similar to the native tissue are required.